{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:31:37Z","timestamp":1791869497944,"version":"4.3.4"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome includes valve leaflet thickening and progressive valve degeneration. However, the underlying mechanisms by which the disease progresses remain undefined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              Mice with\n              <jats:italic toggle=\"yes\">Fibrillin 1<\/jats:italic>\n              gene variant\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              recapitulate histopathologic features of Marfan syndrome, and Wnt (Wingless-related integration site) signaling activity was detected in\n              <jats:italic toggle=\"yes\">TCF\/Lef-lacZ<\/jats:italic>\n              (T-cell factor\/lymphoid enhancer factor-\u03b2-galactosidase) reporter mice. Single-cell RNA sequencing was performed from mitral valves of wild-type and\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice at 1 month of age. Inhibition of Wnt signaling was achieved by conditional induction of the secreted Wnt inhibitor Dkk1 (Dickkopf-1) expression in periostin-expressing valve interstitial cells of\n              <jats:italic toggle=\"yes\">Periostin<\/jats:italic>\n              -Cre;\n              <jats:italic toggle=\"yes\">tetO-Dkk1; R26rtTA; TCF\/Lef-lacZ; Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for ECM (extracellular matrix) and immune cells were performed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Wnt signaling is activated early in mitral valve disease progression, before immune cell infiltration in\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice. Single-cell transcriptomics revealed similar mitral valve cell heterogeneity between wild-type and\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice at 1 month of age. Wnt pathway genes were predominantly expressed in valve interstitial cells and valve endothelial cells of\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice. Inhibition of Wnt signaling in\n              <jats:italic toggle=\"yes\">Fbn1<\/jats:italic>\n              <jats:sup>\n                <jats:italic toggle=\"yes\">C1039G\/+<\/jats:italic>\n              <\/jats:sup>\n              mice at 1 month of age prevented the initiation of MVD as indicated by improved ECM remodeling and reduced valve leaflet thickness with decreased infiltrating macrophages. However, later, Wnt inhibition starting at 2 months did not prevent the progression of MVD.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation but is not responsible for later-stage valve disease progression once it has been initiated. Thus, Wnt signaling contributes to MVD progression in a time-dependent manner and provides a promising therapeutic target for the early treatment of congenital MVD in Marfan syndrome.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320388","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T09:01:14Z","timestamp":1714035674000},"page":"1540-1554","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5387-7760","authenticated-orcid":true,"given":"Na","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Molecular Cardiovascular Biology, the Heart Institute (N.X., C.M.A., K.E.Y.), Cincinnati Children\u2019s Hospital Medical Center, OH."},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, OH (N.X., M.G., K.E.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Division of Molecular Cardiovascular Biology, the Heart Institute (N.X., C.M.A., K.E.Y.), Cincinnati Children\u2019s Hospital Medical Center, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology (Y.Y.), Cincinnati Children\u2019s Hospital Medical Center, OH."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5502-9172","authenticated-orcid":true,"given":"Minzhe","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Neonatology and Pulmonary Biology (M.G.), Cincinnati Children\u2019s Hospital Medical Center, OH."},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, OH (N.X., M.G., K.E.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1444-7124","authenticated-orcid":true,"given":"Katherine E.","family":"Yutzey","sequence":"additional","affiliation":[{"name":"Division of Molecular Cardiovascular Biology, the Heart Institute (N.X., C.M.A., K.E.Y.), Cincinnati Children\u2019s Hospital Medical Center, OH."},{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, OH (N.X., M.G., K.E.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v11.i2.71"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-019-1145-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00558-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.020919"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.082610"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20641"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12881"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000224114.65109.4e"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.07.033"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67789-6"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.1.229"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.181"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22715"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2019.03.033"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310667"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcdd2030200"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.07.734"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.042391"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2017.12.006"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.06.001"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.013896"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.000921"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.02.040"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw229"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20335"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.096560"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58097"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni051"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013693"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.04.041"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20051"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-019-0128-8"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14049"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.173047"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030847"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.130575"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-014-1228-x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.211029"},{"key":"e_1_3_3_44_2","first-page":"190","article-title":"The effect of oxLDL on aortic valve calcification via the Wnt\/","volume":"24","author":"Gao X","year":"2015","unstructured":"Gao, X, Zhang, L, Gu, G, Wu, PH, Jin, S, Hu, W, Zhan, C, Li, J, Li, Y. The effect of oxLDL on aortic valve calcification via the Wnt\/\u03b2-catenin signaling pathway: an important molecular mechanism. J Heart Valve Dis. 2015;24:190\u2013196","journal-title":"J Heart Valve Dis"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304579"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvc.2011.12.001"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900093RR"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2017.12.013"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012050512"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2014-0267"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.001689"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.8.3073"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-009-9136-6"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01986-0"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2015.09.003"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020621"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13132284"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.267103"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.123.320388","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T19:11:14Z","timestamp":1748545874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.123.320388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":57,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1161\/ATVBAHA.123.320388"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.123.320388","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2023-11-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}